Krebs / Citric Acid / TCA Cycle

What are the three names for the same metabolic pathway?

• Citric acid cycle

• Krebs cycle

• TCA cycle

What is the main purpose of the citric acid cycle?

To oxidize acetyl-CoA and capture its energy in NADH, FADH₂, and GTP.

Where does the citric acid cycle occur?

Primarily in the mitochondrial matrix.

Which citric acid cycle enzyme is located in the inner mitochondrial membrane instead of the mitochondrial matrix?

Succinate dehydrogenase.

Does the citric acid cycle directly use oxygen?

No, but it indirectly depends on oxygen so NADH and FADH₂ can be oxidized by the electron transport chain.

Why is the citric acid cycle considered a cycle?

Oxaloacetate is regenerated at the end.

How many times does the citric acid cycle turn per glucose molecule?

Twice, because one glucose produces two acetyl-CoA molecules.

What two molecules combine to begin the citric acid cycle?

Acetyl-CoA and oxaloacetate.

What molecule is formed when acetyl-CoA combines with oxaloacetate?

Citrate.

What are the major products of one turn of the citric acid cycle?

• 3 NADH

• 1 FADH₂

• 1 GTP

• 2 CO₂

What are the major products of the citric acid cycle per glucose molecule?

• 6 NADH

• 2 FADH₂

• 2 GTP

• 4 CO₂

Approximately how many ATP equivalents are produced from one turn of the citric acid cycle?

Approximately 10 ATP equivalents.

What are the citric acid cycle intermediates in order?

Citrate
→ isocitrate
→ α-ketoglutarate
→ succinyl-CoA
→ succinate
→ fumarate
→ malate
→ oxaloacetate

What mnemonic can help remember the citric acid cycle intermediates?

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• Citrate

• Isocitrate

• α-Ketoglutarate

• Succinyl-CoA

• Succinate

• Fumarate

• Malate

• Oxaloacetate

What is the carbon-count pattern of the citric acid cycle?

4 + 2 → 6 → 6 → 5 → 4 → 4 → 4 → 4 → 4

Oxaloacetate has 4 carbons, and acetyl-CoA contributes 2 carbons.

What are the citric acid cycle enzymes in order?

• Citrate synthase

• Aconitase

• Isocitrate dehydrogenase

• α-Ketoglutarate dehydrogenase

• Succinyl-CoA synthetase

• Succinate dehydrogenase

• Fumarase

• Malate dehydrogenase

What enzyme combines acetyl-CoA and oxaloacetate to form citrate?

Citrate synthase.

What enzyme converts isocitrate into α-ketoglutarate?

Isocitrate dehydrogenase.

What enzyme converts α-ketoglutarate into succinyl-CoA?

α-Ketoglutarate dehydrogenase.

What enzyme converts succinate into fumarate and also functions as Complex II of the electron transport chain?

Succinate dehydrogenase.

At which three reactions is NADH produced in the citric acid cycle?

• Isocitrate → α-ketoglutarate

• α-Ketoglutarate → succinyl-CoA

• Malate → oxaloacetate

At which reaction is FADH₂ produced?

Succinate → fumarate.

At which reaction is GTP produced?

Succinyl-CoA → succinate.

At which two reactions is CO₂ released?

• Isocitrate → α-ketoglutarate

• α-Ketoglutarate → succinyl-CoA

What is the order of the energy products produced during the citric acid cycle?

NADH
→ NADH
→ GTP
→ FADH₂
→ NADH

What are the three major regulated enzymes of the citric acid cycle?

• Citrate synthase

• Isocitrate dehydrogenase

• α-Ketoglutarate dehydrogenase

What enzyme is generally considered the rate-limiting enzyme of the citric acid cycle?

Isocitrate dehydrogenase.

What cellular signals generally slow the citric acid cycle?

High ATP and high NADH.

What cellular signals generally speed up the citric acid cycle?

ADP and calcium.

What reaction connects glycolysis to the citric acid cycle?

Pyruvate → acetyl-CoA

This reaction is performed by the pyruvate dehydrogenase complex.

Recite the entire citric acid cycle, including the enzyme and energy product at each step.

1. Oxaloacetate + acetyl-CoA → citrate
   Citrate synthase

2. Citrate → isocitrate
   Aconitase

3. Isocitrate → α-ketoglutarate
   Isocitrate dehydrogenase
   Produces NADH and CO₂

4. α-Ketoglutarate → succinyl-CoA
   α-Ketoglutarate dehydrogenase
   Produces NADH and CO₂

5. Succinyl-CoA → succinate
   Succinyl-CoA synthetase
   Produces GTP

6. Succinate → fumarate
   Succinate dehydrogenase
   Produces FADH₂

7. Fumarate → malate
   Fumarase

8. Malate → oxaloacetate
   Malate dehydrogenase
   Produces NADH

Total per turn: 3 NADH, 1 FADH₂, 1 GTP, and 2 CO₂.